Wallace's first question to both candidates was on the Supreme Court. He asked why Trump believes he is right in confirming a justice before the election and why Biden believes he is right in saying the decision should wait until after Election Day.

"I will tell you very simply, we won the election. Elections have consequences," Trump said. "We have the Senate, we have the White House and we have a phenomenal nominee respected by all top top academic good in every way, good in every way."

"And by the way, the Democrats, they wouldn't even think about not doing it if they have -- the only difference is to try and do it faster. There's no way they would give it up. They had Merrick Garland, but the problem is they didn't have the election so they were stopped."

When the question was given to Biden, he said that the American people have a right to say who the Supreme Court nominee should be and that that nomination should wait until the November election concludes as Americans have already begun voting.

"It's just not appropriate to do this before this election," Biden said. "Roe v. Wade and the Affordable Care Act could both be struck down by a conservative Supreme Court."

Multiple Senate Democrats are refusing to meet with Trump's nominee, Amy Coney Barrett, citing the impending election, and have expressed mounting concern with her stance on health care as the Supreme Court is set to hear arguments on the fate of the Affordable Care Act one week after the election.

Senate Republicans, meanwhile, are moving ahead with the nomination despite claims they made in 2016 about not confirming Garland during an election year.

The first presidential debate of 2020 between Trump and Biden kicked off from Case Western Reserve University and the Cleveland Clinic in Ohio with moderator Chris Wallace of Fox News.

Trump and Biden skipped a handshake, customary at the top of such events, due to the coronavirus precautions. Each walked out to his respective lectern without masks.

The candidates will not deliver opening statements. Instead, the debate has been divided into six roughly 15-minute segments on the following topics selected by Wallace: Trump's and Biden's records, the Supreme Court, COVID-19, the economy, race and violence in U.S. cities, and the integrity of the election.

The entire audience -- already limited in its size -- has been tested for COVID-19.

ABC News Chief Anchor George Stephanopoulos said the main question is whether the candidates will do anything in this debate to change the course of this race.

Editor-in-Chief of FiveThirtyEight Nate Silver said that this presidential race is a "much less close race than it was four years ago."

Biden deputy campaign manager Kate Bedingfield fired back at Donald Trump Jr. -- who did an interview with ABC News ahead of her -- saying the president's son continues to deliver personal attacks on the vice president instead of making the case for why Trump should be reelected.

"I was listening to Don Jr. and I didn't hear a whole lot of reasons to vote for Donald Trump," Bedingfield said. "I heard a lot of attacks. I heard a lot of personal criticisms of Joe Biden's son. I didn't hear a whole lot of reason -- if I'm a voter sitting tonight, listening to this debate -- I didn't hear a lot of reasons to vote for Donald Trump."

Bedingfield said Biden will offer a different choice for voters of a leader focused on the issues, not on attacks, and she said success for the evening will be defined by Biden's ability to connect with "families at their kitchen table."

"He's going to be laying out a concrete vision to make life better for people across this country and I think that the clear contrast between somebody who views the world through the lens of having grown up in Scranton, Pennsylvania, versus somebody who views the world through the lens of Park Avenue is going to be very apparent on the stage tonight," she added.

President Donald Trump is set to enter the first presidential debate on Tuesday down in the polls, but coming off the high of nominating his third Supreme Court justice. Some top advisers expect a dominant performance by the president, despite the opposing narratives of attacks on Joe Biden's mental state and the Trump campaign's work to raise expectations for the Democrat ahead of the showdown.

With days to go the debate, Trump has carried out conflicting and confounding strategies both repeatedly targeting Biden's mental acuity, claiming at a recent rally he doesn't know he's alive, while also making passing attempts to boost the former vice president as a seasoned debater who could outshine him.

"This guy doesn't have a clue. He doesn't know where the hell he is," Trump told his supporters in Pittsburgh a week to the day before the first debate. "This guy doesn't know he's alive."

At a campaign rally Saturday night in Pennsylvania, the president both attacked Biden as "dumb" before immediately lauding him as an experienced debater. "He’s a dumb guy. Always known as a dumb guy. But we look forward to seeing him in the debate. He's got a lot more experience. He's got 47 years. I’ve got 3 1/2 years. So we'll see. But he's got 47 years of experience."

Biden has brushed off Trump's onslaught of attacks on his mental fitness. "Watch me, Mr. President. Watch me. Look at us both, what we say, what we do, what we control, what we know, what kind of shape we're in," the former vice president said when asked by ABC News about the president's attacks on his cognitive ability.

While some advisers tell ABC News they're nervous as the president enters his first debate since his encounters with Hillary Clinton four years ago -- with Biden having participated in nearly a dozen debates leading up to clinching the Democratic nomination -- others are anticipating a knockout performance by the president and expect the debate to help highlight the former vice president's gaffes, sources familiar said.

-ABC News' Will Steakin, Katherine Faulders and John Santucci